Sex modulates the association of fibroblast growth factor 21 with end-stage renal disease in Asian people with Type 2 diabetes: a 6.3-year prospective cohort study

Diabet Med. 2018 Jul;35(7):880-886. doi: 10.1111/dme.13641. Epub 2018 May 2.

Abstract

Aim: To study whether plasma fibroblast growth factor 21 independently predicts the risk of end-stage renal disease in Asian people with Type 2 diabetes.

Methods: In this prospective cohort study, 1700 Asian people with Type 2 diabetes were followed for a mean of 6.3 years in a regional hospital in Singapore. Incident end-stage renal disease was identified by linkage with a national renal registry. The association of baseline fibroblast growth factor 21 levels with risk of progression to end-stage renal disease was studied using survival analyses.

Results: Participants were aged 60 ± 10 years, with an average diabetes duration of 12 years. Their estimated GFR was 73 ± 28 ml/min/1.73 m2 and 62% had albuminuria at baseline. A total of 179 incident end-stage renal disease cases were identified. Plasma fibroblast growth factor 21 interacted with sex in its association with end-stage renal disease (Pinteraction = 0.003). A 1-sd increment in fibroblast growth factor 21 (natural log-transformed) was associated with a 1.32-fold (95% CI 1.05-1.66, P = 0.02) increased hazard for end-stage renal disease in women, after adjustment for traditional risk factors including estimated GFR and albuminuria. Taking death as a competing risk did not materially change the outcome [sub-distribution hazard ratio 1.35 (95% CI 1.11-1.66, P = 0.003)]. Fibroblast growth factor 21 did not predict end-stage renal disease risk in men after adjustment for baseline estimated GFR and albuminuria [hazard ratio 1.07 (95% CI 0.89-1.28, P = 0.49)].

Conclusions: Plasma fibroblast growth factor 21 level independently predicted risk of progression to end-stage renal disease in women with Type 2 diabetes. The pathophysiological relationships among FGF21, sex and renal progression warrant further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Albuminuria
  • Asian People
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / metabolism*
  • Disease Progression
  • Female
  • Fibroblast Growth Factors / metabolism*
  • Glomerular Filtration Rate
  • Humans
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • Singapore / epidemiology

Substances

  • fibroblast growth factor 21
  • Fibroblast Growth Factors